10-71970315-A-G

Variant names:

• chr10-71970315-A-G
• rs874692
• NM_004273.5:c.-108+5621A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000373115.5(CHST3):​c.-108+5621A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 152,150 control chromosomes in the GnomAD database, including 57,209 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.86 (57209 hom., cov: 31)
• Consequence: CHST3 ENST00000373115.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 3 publications found

Genes affected

CHST3 (HGNC:1971): (carbohydrate sulfotransferase 3) This gene encodes an enzyme which catalyzes the sulfation of chondroitin, a proteoglycan found in the extracellular matrix and most cells which is involved in cell migration and differentiation. Mutations in this gene are associated with spondylepiphyseal dysplasia and humerospinal dysostosis. [provided by RefSeq, Mar 2009]

CHST3 Gene-Disease associations (from GenCC):

• spondyloepiphyseal dysplasia with congenital joint dislocations

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000373115.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST3	NM_004273.5	MANE Select	c.-108+5621A>G		intron	N/A	NP_004264.2
	CHST3	NM_001441201.1		c.-108+4840A>G		intron	N/A	NP_001428130.1
	CHST3	NM_001441202.1		c.-108+5415A>G		intron	N/A	NP_001428131.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST3	ENST00000373115.5	TSL:1 MANE Select	c.-108+5621A>G		intron	N/A	ENSP00000362207.4

Frequencies

GnomAD3 genomes AF: 0.865 AC: 131486 AN: 152032 Hom.: 57151 Cov.: 31

Gnomad AFR AF: 0.964

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.792

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.861

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.865 AC: 131602 AN: 152150 Hom.: 57209 Cov.: 31 AF XY: 0.861 AC XY: 64048 AN XY: 74364

African (AFR) AF: 0.965 AC: 40031 AN: 41502

American (AMR) AF: 0.805 AC: 12309 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 2758 AN: 3472

East Asian (EAS) AF: 0.831 AC: 4297 AN: 5172

South Asian (SAS) AF: 0.793 AC: 3819 AN: 4816

European-Finnish (FIN) AF: 0.820 AC: 8687 AN: 10592

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.837 AC: 56917 AN: 67992

Other (OTH) AF: 0.862 AC: 1819 AN: 2110

Alfa AF: 0.842 Hom.: 88529

Bravo AF: 0.868

Asia WGS AF: 0.824 AC: 2863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Benign	0.88
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs874692; hg19: chr10-73730073;